Breast CancerPhase 2NCT02177175
Carvedilol for the Prevention of Anthracycline/Anti-HER2 Therapy Associated Cardiotoxicity Among Women With HER2-Positive Breast Cancer Using Myocardial Strain Imaging for Early Risk Stratification
A Phase 2 study testing Carvedilol in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 2 sites in United States.
Trial summary
The purpose of this study is to find out the effects, good and/or bad, of a beta blocker (carvedilol) on heart function during treatment with anti-HER2 medication(s) including trastuzumab (Herceptin). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Carvedilol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 2 sitesUnited States
- Study dates
- 24 Jun 2014to 24 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female
- Age ≥ 18 years
- Non-metastatic histologically confirmed primary invasive breast carcinoma
- Pathologically confirmed HER2-positive breast cancer
- Scheduled to receive anthracycline chemotherapy followed by anti-HER2 therapy at MSKCC
- Able and willing to provide informed consent
Show all 14Show fewer
- Willing and able to comply with the requirements of the protocol
- Able to swallow capsules
- For Aim 2, all patients must meet the following criteria:
- Meet all inclusion criteria above
- LVEF > 50%
- Abnormal global longitudinal strain (<19%, or a % decrease of ≥ 11% from baseline) prior to initiation of planned anti-HER2 therapy
- Heart rate ≥ 50 beats per minute
- Sitting systolic blood pressure > 90 mmHg
Who cannot join
- Patients are to be excluded from randomization for Aim 2 of this study if they meet any of the following criteria:
- Current treatment with ACE-inhibitors or beta blockers
- Allergies or inability to tolerate beta blockers previously due to bradycardia, hypotension, or AV block.
- Known history of NCI CTCAE (Version 4.0) Grade ≥ 2 symptomatic CHF, myocardial infarction within 12 months prior to randomization, significant symptoms (Grade ≥ 3) relating to left ventricular dysfunction, significant (moderate or severe) valvular disease, or significant cardiac arrhythmia (Grade ≥ 3)
- Pre-menopausal women without a negative serum or urine pregnancy test within 4 weeks of starting treatment
- Enrollment in a therapeutic intervention trial in the Breast Medicine service
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Memorial Sloan Kettering West Harrison
Harrison, New York, 10604
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
The purpose of this study is to find out the effects, good and/or bad, of a beta blocker (carvedilol) on heart function during treatment with anti-HER2 medication(s) including trastuzumab (Herceptin).
Read the detailed description
This phase II placebo-controlled study will evaluate the effect of carvedilol, compared to placebo, on anthracycline/anti-HER2 therapy induced left ventricular dysfunction in patients with HER2-positive breast cancer who are receiving adjuvant or neoadjuvant therapy. All patients will undergo routine cardiac surveillance with 2D echocardiograms per standard of care at multiple time points which will align as closely as possible to the following: pre-anthracycline (baseline), pre-anti-HER2 therapy, and 3, 6, 9, and 12 months (+/- 4 weeks) after initiation of anti-HER2 therapy. In the case that standard of care echocardiograms are not done at these time points, either due to a delay in anti-cancer therapy or due to the patient's medical condition, the principal investigator will determine if the standard of care echocardiogram may be used in lieu of one of the time points listed. Additional speckle tracking strain analysis will be performed on these echocardiograms, and blood specimens will be drawn at several time points for biomarker analysis.
After completion of anthracycline treatment and prior to initiation of anti-HER2 therapy, 32 patients with abnormal myocardial strain, defined as global longitudinal strain < 19% or % change from baseline by > 11%, will be randomized in a 1:1 ratio to carvedilol versus placebo. Carvedilol will be administered twice daily for approximately 1 year OR until the end of anti-HER2 therapy, if it is discontinued prior to 1 year. Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily.
- Conditions
- Breast Cancer
- Being tested
- Carvedilol, placebo
- Keywords
- Carvedilol, Anthracycline, HER2, 14-099
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
placeboOther
| Study group | Role | What they receive |
|---|---|---|
| Carvedilol | Experimental | Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily. Receives: Drug: Carvedilol |
| placebo | Placebo comparator | Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Change in LVEF at 3 Months
Value at 3 months minus value at baseline
Measured: 3 months
Maximum Change in LVEF at 6 Months
Value at 6 months minus value at baseline
Measured: 6 months
Maximum Change in LVEF at 9 Months
Value at 9 months minus value at baseline
Measured: 9 months
Maximum Change in LVEF at 12 Months
Value at 12 months minus value at baseline
Measured: 12 months
Secondary outcomes (1)
Incidence of Abnormal LVEF at 12 Months
The study is designed to detect an intergroup difference of absolute difference of 10 percentage points (simple difference) in the change in LVEF between the experimental and control group. Ten percent is the change in LVEF that is associated with differing degrees of left ventricular dysfunction, and long-term studies among non-cancer patients have shown that outcomes differ among groups of patients who have LVEF differing by 10%.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2014 (estimated)
- Study start24 Jun 2014
- Primary completion24 Jun 2021
- Study completion24 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anthony Yu, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02177175
- Sponsor's protocol ID
- 14-099
- Status last verified
- Jun 2021
- First submitted
- 26 Jun 2014
- Last updated
- 12 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Yu AF, Moore ZR, Moskowitz CS, Liu JE, Dang CT, Ramanathan L, Oeffinger KC, Steingart RM, Schmitt AM. Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer. JAMA Cardiol. 2023 Jul 1;8(7):697-702. doi: 10.1001/jamacardio.2023.1229.
PubMed 37256614
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Carvedilol for the Prevention of Anthracycline/Anti-HER2 Therapy Associated Cardiotoxicity Among Women With HER2-Positive Breast Cancer Using Myocardial Strain Imaging for Early Risk Stratification
- ClinicalTrials.gov ID
- NCT02177175
- Acronym / sponsor ID
- 14-099
- Conditions
- Breast Cancer
- Keywords
- Carvedilol, Anthracycline, HER2, 14-099
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 24 Jun 2014 (actual)
- Primary completion
- 24 Jun 2021 (actual)
- Study completion
- 24 Jun 2021 (actual)
- First posted
- 27 Jun 2014 (estimated)
- Results
- Posted 12 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out the effects, good and/or bad, of a beta blocker (carvedilol) on heart function during treatment with anti-HER2 medication(s) including trastuzumab (Herceptin).
Detailed description
This phase II placebo-controlled study will evaluate the effect of carvedilol, compared to placebo, on anthracycline/anti-HER2 therapy induced left ventricular dysfunction in patients with HER2-positive breast cancer who are receiving adjuvant or neoadjuvant therapy. All patients will undergo routine cardiac surveillance with 2D echocardiograms per standard of care at multiple time points which will align as closely as possible to the following: pre-anthracycline (baseline), pre-anti-HER2 therapy, and 3, 6, 9, and 12 months (+/- 4 weeks) after initiation of anti-HER2 therapy. In the case that standard of care echocardiograms are not done at these time points, either due to a delay in anti-cancer therapy or due to the patient's medical condition, the principal investigator will determine if the standard of care echocardiogram may be used in lieu of one of the time points listed. Additional speckle tracking strain analysis will be performed on these echocardiograms, and blood specimens will be drawn at several time points for biomarker analysis.
After completion of anthracycline treatment and prior to initiation of anti-HER2 therapy, 32 patients with abnormal myocardial strain, defined as global longitudinal strain < 19% or % change from baseline by > 11%, will be randomized in a 1:1 ratio to carvedilol versus placebo. Carvedilol will be administered twice daily for approximately 1 year OR until the end of anti-HER2 therapy, if it is discontinued prior to 1 year. Treatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carvedilol | Experimental | Drug: CarvedilolTreatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily. |
| placebo | Placebo comparator | Other: placeboTreatment in both carvedilol and placebo groups will be systematically up-titrated at weeks 3, 6, and 9 (+/- 1 week) after randomization to a goal dose of 25mg twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Female
- Age ≥ 18 years
- Non-metastatic histologically confirmed primary invasive breast carcinoma
- Pathologically confirmed HER2-positive breast cancer
- Scheduled to receive anthracycline chemotherapy followed by anti-HER2 therapy at MSKCC
Key exclusion criteria (6 listed)
- Patients are to be excluded from randomization for Aim 2 of this study if they meet any of the following criteria:
- Current treatment with ACE-inhibitors or beta blockers
- Allergies or inability to tolerate beta blockers previously due to bradycardia, hypotension, or AV block.
- Known history of NCI CTCAE (Version 4.0) Grade ≥ 2 symptomatic CHF, myocardial infarction within 12 months prior to randomization, significant symptoms (Grade ≥ 3) relating to left ventricular dysfunction, significant (moderate or severe) valvular disease, or significant cardiac arrhythmia (Grade ≥ 3)
- Pre-menopausal women without a negative serum or urine pregnancy test within 4 weeks of starting treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carvedilol | Drug | Carvedilol |
| placebo | Other | placebo |
Primary outcome
Maximum Change in LVEF at 3 Months
Time frame: 3 months
Value at 3 months minus value at baseline
Maximum Change in LVEF at 6 Months
Time frame: 6 months
Value at 6 months minus value at baseline
Maximum Change in LVEF at 9 Months
Time frame: 9 months
Value at 9 months minus value at baseline
Maximum Change in LVEF at 12 Months
Time frame: 12 months
Value at 12 months minus value at baseline
1 secondary outcome
Incidence of Abnormal LVEF at 12 Months
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37256614Yu AF, Moore ZR, Moskowitz CS, Liu JE, Dang CT, Ramanathan L, Oeffinger KC, Steingart RM, Schmitt AM. Association of Circulating Cardiomyocyte Cell-Free DNA With Cancer Therapy-Related Cardiac Dysfunction in Patients Undergoing Treatment for ERBB2-Positive Breast Cancer. JAMA Cardiol. 2023 Jul 1;8(7):697-702. doi: 10.1001/jamacardio.2023.1229.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony Yu, MD principal investigator
Memorial Sloan Kettering Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carvedilol in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Change in LVEF at 3 Months (time frame: 3 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02177175, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2022.